The influence of the prethymic compartment on the acquisition of tolerance to major histocompatibility antigens in the mouse was evaluated by altering this prethymic environment. Thus, strain A bone marrow cells were injected into a lethally irradiated (AxB)F1 mouse. At a later time, the bone marrow from this (AxB)F1 mouse was isolated and re-introduced into a lethally irradiated strain A host. Under conditions which are not now completely understood temporary tolerance to the B haplotype was achieved. To further investigate, the influence of the prethymic environment on the acquisition of tolerance to MHC antigens, (AxB)F1 mice were thymectomized then grafted with a strain A thymus and later irradiated and reconstituted with strain A bone marrow. The engrafted thymus was later tested for the presence of cells bearing the B-haplotype and for reactivity toward this determinant. Preliminary results indicate that although the B haplotype is not present in the thymus, tolerance exists. Therefore, alloreactive patterns in the thymus may be affected by environmental manipulation of the pre-thymic compartment.